BackgroundProgress has been achieved with the introduction of biologics for the management of inflammatory/autoimmune diseases such as rheumatoid arthritis (RA), however such medications induce immune suppression, which is nonselective to the pathogenesis of the disease, resulting in higher rates of infections. Therefore, there are unmet medical needs in the treatment of such diseases, which should be addressed by novel approaches. Accumulating evidence suggests that extracellular vesicles (EVs) play a role in the establishment, maintenance and modulation of autoimmune processes.ObjectivesIn the current study, we hypothesized that isolation of circulating autologous tissue-specific homing EVs from RA patients - may improve the delivery of current FDA-approved anti-inflammatory drugs, which will be encapsulated into these EVs. The drug-loaded EVs will be injected back to the diseased subjects and will naturally find their way to the inflamed tissue.ResultsIndeed, we found that autologous labeled EVs, expressing joint/synovia-specific homing receptors (e.g. αVβ3 integrin), derived from blood of diseased arthritic mice (Collagen antibody-induced arthritis model), can migrate toward the inflamed synovia, usingin vivoimaging system (IVIS). Moreover, we show that these EVs strongly expresses glucose transporter 1 (mGLUT1) which in turn, improve their therapeutic potential to be loaded with anti-inflammatory drugs using glucose-coated gold nanoparticles (GNPs). Finally, we show that EVs derived from plasma of RA patients overexpresses αVβ3 integrin and taken up by LPS/TNFα-induced activated human synovial cell linein vitro.ConclusionOverall, we show the potential of autologous circulating EVs of RA patients to serves as natural nano-carrier for current FDA-approved drugs. We believe that this strategy will increase the specificity and efficiency of current treatment, therefore it will reduce side effects and will improve the quality of life of RA patients and potentially other autoimmune disease patients.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

BackgroundThe exact pathogenesis of fibromyalgia (FM) syndrome is unclear. However, different infections including hepatitis C virus, Human immunodeficiency virus and Lyme disease have already been implicated with the development of FM after their acute phase[1]. Imbalance between pro-inflammatory and anti-inflammatory cytokines has been suggested as a possible mechanism that facilitates the neuropathic pain[2].ObjectivesTo investigate the incidence of FM syndrome among convalesced individuals following hospitalization for Acute Coronavirus Disease-2019 (COVID-19) and to identify possible risk factors.MethodsWe performed a cross-sectional study on patients who were discharged after COVID-19 hospitalization from the Sheba Medical Center, Israel, between July 2020 to November 2020. A phone interview was performed consisting of the following questionnaires: the Fibromyalgia Survey Diagnostic Criteria Questionnaire, Sense of Coherence Questionnaire to evaluate resilience, and the Subjective Traumatic Outlook Questionnaire to assess the associated psychological aspects of the trauma. The incidence of post-COVID FM was calculated and regression models were performed to identify predictors.ResultsThe study population consisted of 198 eligible patients who completed the phone interview. The median age was 64 (52-72) and 37% were women. The median follow-up was 5.2 months (IQR 4.4-5.8). The incidence of FM was 15% (30 patients) and 87% (172 patients) had at least one FM-related symptom. Female gender was significantly associated with post-COVID FM (OR 3.65, p=0.002). In addition, high median Subjective Traumatic Outlook scores and low median Sense of Coherence scores were both significantly associated with post-COVID FM (OR 1.19, p<0.001 and OR 0.92, p<0.001, respectively).ConclusionFM is highly prevalent among COVID-19 convalescent patients. Our finding suggests that a significant subjective traumatic experience and a low resilience are highly associated with post-COVID FM.References[1]Buskila D, Atzeni F, Sarzi-Puttini P. Etiology of fibromyalgia: the possible role of infection and vaccination. Autoimmun Rev. 2008;8: 41-43.https://doi.org/10.1016/j.autrev.2008.07.023[2]Amital M, Ben-Shabat N, Amital H, Buskila D, Cohen AD, Amital D. COVID-19 associated hospitalization in 571 patients with fibromyalgia—A population-based study. PLoS ONE. 2021:16: e0261772.https://doi.org/10.1371/journal.pone.0261772Acknowledgements:NIL.Disclosure of InterestsNone Declared.

BackgroundIn acute COVID-19 infection, growing evidence hints towards a broad activation of plasma cells and the presence of pathologic autoantibodies (abs). A systematic screening for abs confirmed induction of diverse functional abs by SARS-CoV-2 infection (1, 2). Immune-mediated thrombosis, involving platelet activation, has been identified as one of the key pathogenic mechanisms in COVID-19 and is linked to morbidity and mortality (3). As natural abs against G protein-coupled receptors, functional abs against the thrombin receptor type-1 (PAR-1) might predispose for increased activation of the coagulation system present in COVID-19 infection.ObjectivesThe aim of this study is to identify the diagnostic value of anti-PAR1 antibodies and their capacity to predict the outcome of COVID-19 infection.Methods82 serum samples from 55 individuals with COVID-19 derived from three different hospitals in Schleswig-Holstein, Germany, and 88 single time point samples from healthy controls were subjected to ELISA-based quantification of anti-PAR-1 abs (CellTrend GmbH Luckenwalde, Germany). The levels of anti-AT1R abs were compared with clinical and laboratory parameters.ResultsCOVID-19 patients revealed markedly increased levels of circulating anti-PAR1 abs in hospitalized patients particularly in those required intensive care treatment in comparison to controls (p < 0.0001, Figure 1a). Anti-PAR1 ab levels were highest in patients with fatal outcome (p = 0.006, Figure 1a). Receiver operating characteristic (ROC) analysis of PAR1 abs levels in COVID-19 patients revealed a sensitivity of 84.00% and a specificity 79.25% for patients requiring intensive care unit (ICU) treatment and a sensitivity of 87.50 % and a specificity 84.51 % to distinguish fatal vs. non-fatal disease outcome (Figure 1b). We found correlation of circulating anti-PAR1 abs with D dimers.Figure 1.Levels of anti-PAR-1 abs in healthy controls (HC) versus COVID-19 positive patients with different disease severity and in non survivors (left). ROC curves are shown to discriminate patients requiring intensive care unit (ICU) or survivors in COVID-19 infection.ConclusionThe increased anti-PAR1 abs, their prediction to identify patients requiring ICU and fatal outcome, and the correlation with markers for blood clotting suggest a role for antibodies against PAR1 in the disease development of blood clotting in COVID-19.References[1]Bastard P, Rosen LB, Zhang Q, et al. Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science 2020: 370(6515).[2]Wang EY, Mao T, Klein J, et al. Diverse functional autoantibodies in patients with COVID-19. Nature 2021.[3]Bonaventura A, Vecchie A, Dagna L, et al. Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19. Nat Rev Immunol 2021: 21(5): 319-329.Disclosure of InterestsNone declared